A balanced (1;11)(q42.1;q14.3) translocation segregates with schizophrenia and related psychiatric disorders in a large Scottish family (maximum LOD = 6.0). We hypothesize that the translocation is the causative event and that it directly disrupts gene function. We previously reported a dearth of genes in the breakpoint region of chromosome 11 and it is therefore unlikely that the expression of any genes on this chromosome has been affected by the translocation. By contrast, the corresponding region on chromosome 1 is gene dense and, not one, but two novel genes are directly disrupted by the translocation. These genes have been provisionally named Disrupted-In-Schizophrenia 1 and 2 ( DISC1 and DISC2 ). DISC1 encodes a large protein with no significant sequence homology to other known proteins. It is predicted to consist of a globular N-terminal domain(s) and helical C-terminal domain which has the potential to form a coiled-coil by interaction with another, as yet, unidentified protein(s). Similar structures are thought to be present in a variety of unrelated proteins that are known to function in the nervous system. The putative structure of the protein encoded by DISC1 is therefore compatible with a role in the nervous system. DISC2 apparently specifies a non-coding RNA molecule that is antisense to DISC1, an arrangement that has been observed at other loci where it is thought that the antisense RNA is involved in regulating expression of the sense gene. Altogether, these observations indicate that DISC1 and DISC2 should be considered formal candidate genes for susceptibility to psychiatric illness.

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Two overlapping and antiparallel genes on chromosome 1, Disrupted In Schizophrenia 1 and 2 (DISC1 and DISC2), are disrupted by a (1;11)(q42.1;q14.3) translocation which segregates with schizophrenia through at least four generations of a large Scottish family. Consequently, these genes are worthy of further investigation as candidate genes potentially involved in the aetiology of major psychiatric illness. We have constructed a contiguous clone map of PACs and cosmids extending across at least 400 kb of the chromosome 1 translocation breakpoint region and this has provided the basis for examination of the genomic structure of DISC1. The gene consists of thirteen exons, estimated to extend across at least 300 kb of DNA. The antisense gene DISC2 overlaps with exon 9. Exon 11 contains an alternative splice site that removes 66 nucleotides from the open reading frame. The final intron of DISC1 belongs to the rare AT-AC class of introns. We have also mapped marker DIS251 in close proximity to DISC1, localising the gene within a critical region identified by several independent studies. Information regarding the structure of the DISC1 gene will facilitate assessment of its involvement in the aetiology of major mental illness in psychotic individuals unrelated to carriers of the translocation. Molecular Psychiatry (2001) 6, 173-178.

Deceived December Id, ldtí'iThe antibacterial activity of sets of alcohols, amines, phenols, alkyl-h-naphthols, aromatic ami aliphatic isothiocyanates, diguanidines, diamidines, phenyl methacrylates, N'-alkyli 1 iket-hamide chlorides, arylnitroalkenes, ureas, benzyl alcohols, alkyl sulfates, «-bromo and «-hydroxy soaps, and quinine derivatives has been correlated with their chemical structure. It is shown by means of substituent constants and regression analysis that the lipophilic character of the molecule or substituent as expressed by log P or is the most important, factor in determining the activities of the compounds examined. The ideal lipophilic character (log P0) for gram-negative cells has been found to be about 4, but that for gram-positive cells is about 6. Where linear dependence on log P or it is observed (less than supraoptimal lipophilic character was studied), the slope relating log Bit and lug P or is about 0.7. This is very close to that found for the equation correlating the binding of phenols by bovine serum albumin. This work clearly shows the great advantage in using the octanol-water reference system for comparing the dependence of biological activity on hydrophobic character of work of different investigators vising different sets of drugs in different biological systems.